Actively Recruiting
Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME with Lymphodepleting Chemotherapy for Relapsed/Refractory Myeloid Malignancies
Led by M.D. Anderson Cancer Center · Updated on 2025-12-23
44
Participants Needed
1
Research Sites
104 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating PRAME-TCR-NK cells, a type of engineered T cell receptor-modified natural killer cell therapy, combined with lymphodepleting chemotherapy to treat patients with relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemia (CMML). This phase I/II study aims to find the best dose that balances safety and effectiveness while monitoring response rates and treatment failure over time. The treatment includes several chemotherapy drugs given before the cell therapy infusion. Patients receive dexamethasone by mouth on days -10 to -6, decitabine intravenously on days -6 to -4, fludarabine and cyclophosphamide intravenously on days -5 to -3, and then the PRAME-TCR-NK cells intravenously on day 0. The study tests up to four increasing dose levels of the NK cells, starting with the lowest dose and increasing if side effects are tolerable. Participants undergo various assessments including heart scans, imaging, bone marrow biopsies, and blood tests before and throughout the study. They are followed for 24 months after treatment and then for at least 15 years to monitor safety and long-term outcomes. Researchers also study immune recovery and quality of life using questionnaires. The main focus is on safety and adverse events over about one year.
CONDITIONS
Brief Title
Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 18 and 80 years
- Diagnosed with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemia (CMML)
- At least 7 days since last cytotoxic chemotherapy, except hydroxyurea allowed until day before lymphodepleting chemotherapy
- Karnofsky Performance Scale score above 50%
- Adequate kidney, liver, heart, and lung function as defined by specific lab and clinical criteria
- Able to provide written informed consent
- Use effective birth control during and up to 3 months after study therapy for participants who can have children
- Life expectancy of at least 3 months
- Positive for HLA-A*02:01 type
- For AML: relapsed or refractory disease after at least two prior therapies including hypomethylating agents and venetoclax
- For MDS/CMML: high or intermediate risk with at least two prior therapies or relapse after treatment
- Signed consent for long-term follow-up protocol
You will not qualify if you...
- Positive pregnancy test in females of childbearing potential
- Grade 3 or higher toxicity from previous treatment
- Uncontrolled infections not responding to therapy
- Active hepatitis B or C infection
- HIV with detectable viral load
- Active neurological disorders
- Active autoimmune disease within past 12 months
- Active brain or meningeal involvement by cancer
- Active graft-versus-host disease requiring treatment
- Other active malignancies except treated cervical or non-melanoma skin cancers
- Serious medical conditions endangering safety
- Major surgery within 4 weeks before chemotherapy
- Allogeneic stem cell transplant or donor lymphocyte infusion within 12 weeks before chemotherapy
- Use of other investigational or anti-cancer agents
- Current systemic steroid therapy beyond physiologic doses or recent immunosuppressive treatments
- Use of immunosuppressive drugs such as calcineurin inhibitors
- Rapidly progressing AML or MDS
- Inability to stop steroid treatment within 24 hours of cell infusion
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 screening and enrollment visit
Duration - 10 days
Participants receive lymphodepleting chemotherapy with dexamethasone, decitabine, fludarabine, and cyclophosphamide before receiving the study treatment.
Multiple visits during days -10 to -3 for chemotherapy administration
Duration - 1 day
Participants receive engineered T cell receptor-modified natural killer (TCR-NK) cells targeting PRAME as the investigational therapy.
1 visit for TCR-NK cell infusion on day 0
Duration - Up to 15 years
Participants are followed up for safety, response, and long-term outcomes after treatment completion.
Regular follow-up visits during the first 24 months and long-term monitoring thereafter
Trial Site Locations
Total: 1 location
1
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
Research Team
J
Jeremy Ramdial, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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